Title
The [4Fe4S] cluster of human DNA primase functions as a redox switch using DNA charge transport
Author
Elizabeth O’Brien, Marilyn E. Holt, Matthew K. Thompson, Lauren E. Salay, Aaron C. Ehlinger, Walter J. Chazin, Jacqueline K. Barton
Year
2017
Journal
Science
Abstract
DNA charge transport chemistry offers a means of long-range, rapid redox signaling. We demonstrate that the [4Fe4S] cluster in human DNA primase can make use of this chemistry to coordinate the first steps of DNA synthesis. Using DNA electrochemistry, we found that a change in oxidation state of the [4Fe4S] cluster acts as a switch for DNA binding. Single-atom mutations that inhibit this charge transfer hinder primase initiation without affecting primase structure or polymerization. Generating a single base mismatch in the growing primer duplex, which attenuates DNA charge transport, inhibits primer truncation. Thus, redox signaling by [4Fe4S] clusters using DNA charge transport regulates primase binding to DNA and illustrates chemistry that may efficiently drive substrate handoff between polymerases during DNA replication.
Instrument
J-810
Keywords
Circular dichroism, Secondary structure, Biochemistry